title: Contribution of electrostatic and structural properties of Kv4.3 S4 arginine residues to the regulation of channel gating.
abstract: Previous work has demonstrated that replacing individual arginine (R) residues in the S4 domain of Kv4.3 with alanine (A) not only altered activation and deactivation processes, but also those of closed-state inactivation (CSI) and recovery. R-->A mutants eliminated individual positive charge while substantially reducing side chain volume and hydrophilic character. Their novel effects on gating may thus have been the result of electrostatic and/or structural perturbations. To address this issue, and to gain further insights into the roles that S4 plays in the regulation of Kv4.3 gating transitions, we comparatively analyzed arginine to glutamine (R-->Q) mutations at positions 290, 293, and 296. This maneuver maintained positive charge elimination of the R-->A mutants, while partially restoring native side chain volume and hydrophilic properties. R-->A and R-->Q mutant pairs produced similar effects on the forward gating process of activation. In contrast, significant differences between the two substitutions were discovered on deactivation, CSI, and recovery, with the R-->Q mutants partially restoring wild type characteristics. Our results argue that modification of individual S4 residue properties may result in altered localized interactions within unique microenvironments encountered during forward and reverse gating transitions. As such, predominant effects appear on the reverse gating transitions of deactivation and recovery. These results are consistent with the proposal that arginine residues in S4 are involved in regulating Kv4.3 CSI and recovery.
authors.affiliation: University at Buffalo, State University of New York School of Medicine and Biomedical Sciences, Department of Physiology and Biophysics, Buffalo, New York 14214, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Skerritt
authors.forename: Donald L
authors.initials: DL
authors.lastname: Campbell
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D055724:Electrophysiological Phenomena; D005260:Female; D005289:Ferrets; D015640:Ion Channel Gating; D007700:Kinetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009865:Oocytes; D018408:Patch-Clamp Techniques; D051672:Shal Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity; D014982:Xenopus laevis
chemical_list: D051672:Shal Potassium Channels; D001120:Arginine